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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1967
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH - Refer to Section 13.2 for read-across justification document

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1967
Report date:
1967

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
Deviations:
not applicable
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Reference substance name:
sodium lauryl sulphate
IUPAC Name:
sodium lauryl sulphate
Test material form:
not specified
Details on test material:
- Name of test material (as cited in study report): sodium lauryl sulphate
- Physical state: no data
- Analytical purity: 86% a.s.
- Lot/batch No.: no data
- Supplier: Egham Industrial Chemical Laboratory, "Shell" Research Ltd.

Test animals

Species:
rat
Strain:
other: Carworth Farm 'E' strain
Details on species / strain selection:
Inhouse laboratory culture.
Pathogen-free.
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Inhouse culture
- Females (if applicable) nulliparous and non-pregnant: Not reported
- Age at study initiation: 5 weeks
- Weight at study initiation: 150-250 g
- Fasting period before study: No
- Housing: Not reported
- Diet (e.g. ad libitum): Ad lib
- Water (e.g. ad libitum): Ad lib
- Acclimation period: Not reported

DETAILS OF FOOD AND WATER QUALITY: Diet = Diet 86 powder (Withers Ltd., Godalming, Surrey)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not reported
- Humidity (%): Not reported
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): Not reported

IN-LIFE DATES: From: To: Not reported

Administration / exposure

Route of administration:
oral: feed
Details on route of administration:
Rats were fed dietary levels of 40, 200, 1000 or 5000 ppm active material (corresponding to 3, 17, 86 and 430 mg/kg bw/day actual ingested) for 13 weeks. Control groups received Diet 86 powder (Withers Ltd., Godalruing, Surrey).
Vehicle:
not specified
Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: Not reported

- DIET PREPARATION
- Rate of preparation of diet (frequency): Not reported
- Mixing appropriate amounts with (Type of food): Not reported
- Storage temperature of food: Not reported

- VEHICLE
- Justification for use and choice of vehicle (if other than water): Not reported
- Concentration in vehicle: Not reported
- Amount of vehicle (if gavage): N/A
- Lot/batch no. (if required): Not reported
- Purity: Not reported
Analytical verification of doses or concentrations:
no
Details on analytical verification of doses or concentrations:
N/A
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
Diet provided ad libitum
Doses / concentrationsopen allclose all
Dose / conc.:
40 ppm
Dose / conc.:
200 ppm
Dose / conc.:
1 000 ppm
Dose / conc.:
5 000 ppm
No. of animals per sex per dose:
12 male and 12 female per test treatment group
18 male and 18 female per test Control group
Control animals:
yes, plain diet
Details on study design:
- Dose selection rationale: From previous literature (Smyth, Seaton & Fischer, 1941; Fitzhugh & Nelson, 1948; Fitzhugh, Schouboe & Nelson, 1960; Tusing, Paynter, Opdyke & Snyder, 1962).
- Rationale for animal assignment (if not random): Not reported
- Rationale for selecting satellite groups: N/A
- Post-exposure recovery period in satellite groups: N/A
- Section schedule rationale (if not random): N/A
Positive control:
N/A

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily

BODY WEIGHT: Yes
- Time schedule: Weekly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Mean weekly food intake per treatment group calculated

FOOD EFFICIENCY: No

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes (Haemoglobin, packed cell volume, red blood cell, white blood cell)
- Time schedule for collection of blood: Study terminus
- Anaesthetic used for blood collection: No
- Animals fasted: Not specified
- How many animals: 12 males and 12 females from each test group and 18 males and 18 females from control groups

CLINICAL CHEMISTRY: Yes (urea, protein)
- Time schedule for collection of blood: Study terminus
- Animals fasted: Not specified
- How many animals: 12 males and 12 females from each test group and 18 males and 18 females from control groups.

URINALYSIS: Yes (pH, osmolarity reported and colour, protein, reducing substances and bile salts found to be negative in all test groups)
- Time schedule for collection of urine: Week 12 for 5000 ppm and control groups only
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Not specified

NEUROBEHAVIOURAL EXAMINATION: No

IMMUNOLOGY: No

OTHER: N/A
Sacrifice and pathology:
GROSS PATHOLOGY: Yes, mean organ weights reported (brain (adjusted for initial body weight), heart, liver, spleen, kidneys, testes)

HISTOPATHOLOGY: Yes, sections of organs taken from control and 5000 ppm groups.
Other examinations:
N/A
Statistics:
Statistical analyses of terminal body weights, food intakes and organ weights were made using the initial body weight as a covariate in covariance analysis.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
effects observed, non-treatment-related
Description (incidence and severity):
A statistically significant increse in Hb, PCV (p ≤ 0.05) and RBC (p ≤ 0.01) was observed in the blood samples collected from female rats treated with 40 ppm. In the absence of a dose response at higher test concentrations, the effects cannot be attributed to a test item related response.
Clinical biochemistry findings:
effects observed, non-treatment-related
Description (incidence and severity):
Increase serum urea concentration in females on 5000 ppm and increase in serum total concentration in males on 5000 ppm
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Significant increases in absolute organ weights were confined to the highest test group (5000 ppm) however only the increased liver weights from the females were found to be statistically significantly (p ≤ 0.05)
Gross pathological findings:
no effects observed
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
effects observed, non-treatment-related
Description (incidence and severity):
Spontaneous lesions, mainly hydronephrosis, were present in all groups of animals.
Histopathological findings: neoplastic:
not examined
Other effects:
not examined
Details on results:
In conclusion, treatment with the test item at 40, 200, 1000 and 5000 ppm had no definite effect on mortality, clinical condition, body weight gain, feeding, haematology or urinalysis. Increases in absolute organ weights were confined to the highest test group (5000 ppm) however only the increased liver weights from the females were found to be statistically significantly (p ≤ 0.05). The increase in organ weights at the highest tested concentration (5000 ppm) were unaccompanied by any pathological effects, as a result, 5000 ppm is considered a no-observed effect level (NOAEL) for the test item.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
5 000 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
organ weights and organ / body weight ratios
Key result
Dose descriptor:
NOAEL
Effect level:
> 430 mg/kg bw/day (actual dose received)
Based on:
test mat.
Remarks:
actual dose received
Sex:
male/female
Basis for effect level:
organ weights and organ / body weight ratios

Target system / organ toxicity

Critical effects observed:
no

Any other information on results incl. tables

Table 3       Mean body weights and body weight gains/ losses

 

Dietary intake

(ppm)

Male

Female

Body weight (g) at week

Mean weekly food intake (g)

Body weight (g) at week

Mean weekly food intake (g)

4

8

13

4

8

13

0

243

319

359

139

172

213

227

107

40

246

323

363

140

175

215

233

108

200

239

315

348

138

170

213

225

104

1000

234

308

351

133

175

216

228

111

5000

243

319

365

139

169

213

226

106

Body weights are adjusted for initial body weight

For test groups (n=12) and for control groups (n=18)

 

Table 4       Mean haematological examination results

 

Dietary intake

(ppm)

Male

Female

Hb

(g/100 mL)

PCV

(%)

RBC

(108/mm8)

WBC

(108/mm8)

Hb

(g/100 mL)

PCV

(%)

RBC

(108/mm8)

WBC

(108/mm8)

0

14.4

46.2

-

-

14.1

42.8

6.52

4.8

40

14.5

46.0

-

-

14.7*

45.3*

7.01**

4.9

200

14.5

47.4

-

-

14.1

45.3

6.77

4.6

1000

14.6

46.6

-

-

13.7

41.9

6.47

4.0

5000

14.5

46.1

-

-

14.6

43.7

6.74

4.5

Hb (haemoglobin); PCV (packed cell volume); RBC (red blood cell); WBC (white blood cell)

- RBC and WBC for males was disregarded due to a fault with the measuring device

For test groups (n=12) and for control groups (n=18)

* (p ≤0 0.05); ** (p ≤ 0.01)

 

Table 5       Mean serum chemistry and urine analysis

 

Dietary intake

(ppm)

Male

Female

Serum chemistry

Urine analysis

Serum chemistry

Urine analysis

Urea

(g/100 mL)

Protein

(g/100 mL)

pH

Osmolarity

(mosmoles)

Urea

(g/100 mL)

Protein

(g/100 mL)

pH

Osmolarity

(mosmoles)

0

52

6.4

7.1

2003

56

6.3

6.3

1840

40

51

6.3

-

-

58

6.2

-

-

200

53

6.2

-

-

54

6.2

-

-

1000

53

6.2

-

-

60

6.0

-

-

5000

54

6.3

6.7

2054

53

6.5

6.2

1870

Test for blood, bile salts and reducing substances were negative in all groups

- Not examined

For test groups (n=12) and for control groups (n=18)

 

Table 6       Absolute organ weights (g)

 

Dietary intake

(ppm)

Male

Female

B.W.

Brain

Heart

Liver

Spleen

Kidneys

Testes

B.W.

Brain

Heart

Liver

Spleen

Kidneys

0

359

1.96

0.98

13.71

0.66

2.40

3.51

228

1.86

0.70

8.53

0.50

1.55

40

363

1.96

0.98

13.02

0.67

2.43

3.45

233

1.88

0.72

7.82

0.50

1.60

200

348

1.95

0.96

12.85

0.66

2.31

3.47

225

1.84

0.68

8.62

0.51

1.58

1000

351

1.97

0.98

13.33

0.68

2.34

3.42

228

1.88

0.67

8.24

0.50

1.57

5000

365

1.98

0.98

13.70

0.66

2.34

3.48

226

1.83

0.70

9.30*

0.51

1.59

Values are means, except brain, adjusted for initial body weight of groups of 12 test and 18 control animals

B.W. (terminal body weight)

* (p ≤ 0.05)

Applicant's summary and conclusion

Conclusions:
In conclusion, treatment with the test item at 40, 200, 1000 and 5000 ppm had no definite effect on mortality, clinical condition, body weight gain, feeding, haematology or urinalysis. Increases in absolute organ weights were confined to the highest test group (5000 ppm) however only the increased liver weights from the females were found to be statistically significant (p ≤ 0.05). The increase in organ weights at the highest tested concentration (5000 ppm) was unaccompanied by any pathological effects, as a result, 5000 ppm is considered a no-observed effect level (NOAEL) for the test item.

This result is appropriate under a read-across approach for applicability to the target substance sodium octane-1-sulphonate monohydrate.
Executive summary:

The purpose of this test was to assess the systemic toxicity potential of sodium lauryl sulphate following repeated exposure to 12 male and 12 female Carwoth Farm ‘E’ strain in rats by dietary administration at dose levels of 40, 200, 1000 and 5000 ppm for up to 13 weeks.

 

A summary of adult responses to the test item are described below;

 

Mortality- no treatment related effects were observed.

 

Clinical signs- no treatment related effects were observed.

 

Bodyweight- no treatment related effects were observed.

 

Food consumption and efficiency- no treatment related effects were observed.

 

Haematology and urinalysis-no treatment related effects were observed

 

Organ weights- Significant increases in absolute organ weights were confined to the highest test group (5000 ppm) however only the increased liver weights from the females were found to be statistically significant (p ≤ 0.05).

 

Histopathology- The increase in organ weights at the highest tested concentration (5000 ppm) were unaccompanied by any pathological effects.

 

In conclusion, treatment with the test item at 40, 200, 1000 and 5000 ppm (corresponding to 3, 17, 86 and 430 mg/kg bw/day actual ingested) had no definite effect on mortality, clinical condition, body weight gain, feeding, haematology or urinalysis. Increases in absolute organ weights were confined to the highest test group (5000 ppm) however only the increased liver weights from the females were found to be statistically significant (p ≤ 0.05). The increase in organ weights at the highest tested concentration (5000 ppm) was unaccompanied by any pathological effects, as a result, 5000 ppm (430 mg/kg bw/d) is considered a no-observed effect level (NOAEL) for the test item.

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